The purpose of these studies is to define the neurohormonal control of esophageal motility in order to provide an understanding of the pathogenesis of esophageal motor disorders. We use the opossum as an experimental model because of the similarity of the opossum esophagus to that of man. We have developed a vagus nerve-lower esophageal sphincter pressure preparation in vivo. Using this preparation, we have shown that vagus nerves provide inhibitory innervation to the lower esophageal sphincter. The vagal pathway consists of preganglionic neurons which are cholinergic and postganglionic neurons which are neither cholinergic nor adrenergic. We have also shown that nicotine acts to inhibit lower esophageal sphincter pressure. We have also shown that circulating gastrin is is not responsible for resting sphincter pressure. Now, studies are planned to: a) investigate the role of tonic neural activity in the genesis of basal sphincter pressure; b) examination of the candidate agents which may be the transmitters of the postganglionic inhibitory neurons; and c) influence of adrenergic stimulation of the vagal activity on the sphincter. BIBLIOGRAPHIC REFERENCES: Goyal, R.K., and Rattan, S.: Nature of vagal inhibitory innervation to the lower esophageal sphincter. J. Clin. Invest. 55:1119-1126, 1975. Rattan S., and Goyal, R.K.: Effect of nicotine on the lower esophageal sphincter: Studies on the mechanism of action. Gastroenterology 69:154-159, 1975.